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1.
Artigo em Inglês | MEDLINE | ID: mdl-32040220

RESUMO

Mycosis fungoides (MF) is the most common cutaneous lymphoma. Narrow-band ultraviolet B (nbUVB) therapy has become the first-line treatment for early-stage MF (stage IA, IB, and IIA). However, more studies are needed to determine better maintenance regimens to postpone disease relpase.

2.
Clin Infect Dis ; 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31900472

RESUMO

We report two generalized verrucosis (GV) patients homozygous for a novel mutation in the start codon of IL7. Unlike the previous report in which IL-7 deficiency accompanied CD4 T lymphocytopenia, circulating CD4 T-cells were not depleted in one of our patients, suggesting a GV pathogenesis other than poor T-cell development.

3.
J Dermatol ; 47(1): 41-46, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31646683

RESUMO

Acne keloidalis (AK) is one of the primary cicatricial alopecias and predominantly affects men of African descent. Reports in Asians are scant. This study aimed to retrospectively review the clinical and histopathological features of AK patients in southern Taiwan and identify the pathognomonic features of AK. There were 15 patients with histopathologically confirmed AK in National Cheng Kung University Hospital between 1988 and 2018. The median onset age was 24 years (range, 14-71). The male : female ratio was 14:1. In the acute stage of AK, the lymphocytic and neutrophilic peri-infundibular inflammatory infiltrates with microabscess formation and edema corresponded to the clinical finding of isolated papules or pustules. Subsequently, the inflammatory infiltrates involved the mid-dermis and the isthmus of hair follicles. The "spade sign", a thin and dilated space resembling the shape of a balloon or spade symbol of playing cards at the level of lower isthmus, was identified in eight biopsies from five patients and may be a pathognomonic sign in the subacute stage of AK. At the chronic stage, the segments of hair shafts remained in the upper to mid-dermis and induced chronic inflammation and extensive fibrosis, resulting in the clinical keloid-like appearance. The restriction of inflammation and fibrosis in the upper to mid-dermis was another unique and pathognomonic feature of AK.

4.
Int J Dermatol ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31763692

RESUMO

BACKGROUND: Paronychia is a common adverse event caused by epidermal growth factor receptor (EGFR) inhibitors. However, high rates of post-treatment discomfort, infection, recurrence, and increased time to return to work have been noted after nail plate avulsion for EGFR inhibitor-induced paronychia. Furthermore, poor wound healing and malnutrition were common conditions found in cancer patients. The aim of this study is to find an effective, pain-relieving, and noninvasive treatment for patients with severe paronychia induced by EGFR inhibitors. METHODS: Data from a series of 35 non-small cell lung cancer cases suffering from EGFR inhibitor-induced paronychia with pyogenic granuloma-like lesions of digits treated with betaxolol 0.25% ophthalmic solution once daily were collected and analyzed. RESULTS: Of the 35 patients suffering from grade 2 or 3 paronychia with pyogenic granuloma-like lesions induced by EGFR inhibitors, 34 (97.1%) demonstrated complete resolution and only one (2.9%) had partial resolution after 12 weeks of topical betaxolol treatment. The grading of paronychia according to the Common Terminology Criteria for Adverse Events decreased from an average of 2.29 to 0.63 after 4 weeks of treatment (P = 5.55 × 10-16 ). All the patients had significant improvement (50% pain reduction), as their pain visual analogue scale scores decreased from an average of 7.06 to 2.26 after one week of treatment (P = 6.11 × 10-25 ). CONCLUSION: Betaxolol 0.25% ophthalmic solution is an effective, safe, and pain-relieving treatment for patients suffering from EGFR inhibitor-induced paronychia with pyogenic granuloma-like lesions and deep fissures.

5.
Br J Cancer ; 121(11): 973-978, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31673105

RESUMO

BACKGROUND: The antihypertensive agent hydrochlorothiazide has been associated with increased risks of non-melanoma skin cancer (NMSC) and possibly some melanoma subtypes. Previous studies were, however, conducted in predominantly Caucasian populations. We therefore examined the association between hydrochlorothiazide and skin cancer risk in an Asian population. METHODS: By using Taiwan's National Health Insurance Research Database (NHIRD), we conducted three separate case-control studies of lip cancer, non-lip non-melanoma skin cancer and melanoma. Cases (n = 29,082) with a first-ever skin cancer diagnoses (2008-2015) were matched 1:10 to population controls. We estimated odds ratios (ORs) associating hydrochlorothiazide use with skin cancer risk by using conditional logistic regression. RESULTS: Hydrochlorothiazide use showed no overall association with any of the three outcomes: ORs for high cumulative use of HCTZ (≥50,000 mg) were 0.86 (95% CI 0.09-7.81) for lip cancer, 1.16 (95% CI 0.98-1.37) for non-lip NMSC and 1.07 (95% CI 0.65-1.76) for melanoma. There was some evidence of a dose-response pattern for non-lip NMSC, with an OR of 1.66 (95% CI 0.82-3.33) for 100,000-149,999 mg of HCTZ. The null findings were robust across subgroup and sensitivity analyses. CONCLUSION: Use of HCTZ appears safe in terms of skin cancer risk in an Asian population.

6.
J Invest Dermatol ; 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31493396

RESUMO

Dermatofibromas are common benign skin lesions, the etiology of which is poorly understood. We identified two unrelated pedigrees in which there was autosomal dominant transmission of multiple dermatofibromas. Whole exome sequencing revealed a rare shared heterozygous missense variant in the F13A1 gene encoding factor XIII subunit A (FXIII-A), a transglutaminase involved in hemostasis, wound healing, tumor growth, and apoptosis. The variant (p.Lys679Met) has an allele frequency of 0.0002 and is predicted to be a damaging mutation. Recombinant human Lys679Met FXIII-A demonstrated reduced fibrin crosslinking activity in vitro. Of note, the treatment of fibroblasts with media containing Lys679Met FXIII-A led to enhanced adhesion, proliferation, and type I collagen synthesis. Immunostaining revealed co-localization between FXIII-A and α4ß1 integrins, more prominently for Lys679Met FXIII-A than the wild type. In addition, both the α4ß1 inhibitors and the mutation of the FXIII-A Isoleucine-Leucine-Aspartate-Threonine (ILDT) motif prevented Lys679Met FXIII-A-dependent proliferation and collagen synthesis of fibroblasts. Our data suggest that the Lys679Met mutation may lead to a conformational change in the FXIII-A protein that enhances α4-integrin binding and provides insight into an unexpected role for FXIII-A in the pathobiology of familial dermatofibroma.

7.
Cancer Cell ; 36(2): 168-178.e4, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31327656

RESUMO

Reactivation of T cell immunity by PD-1/PD-L1 immune checkpoint blockade has been shown to be a promising cancer therapeutic strategy. However, PD-L1 immunohistochemical readout is inconsistent with patient response, which presents a clinical challenge to stratify patients. Because PD-L1 is heavily glycosylated, we developed a method to resolve this by removing the glycan moieties from cell surface antigens via enzymatic digestion, a process termed sample deglycosylation. Notably, deglycosylation significantly improves anti-PD-L1 antibody binding affinity and signal intensity, resulting in more accurate PD-L1 quantification and prediction of clinical outcome. This proposed method of PD-L1 antigen retrieval may provide a practical and timely approach to reduce false-negative patient stratification for guiding anti-PD-1/PD-L1 therapy.

8.
J Cosmet Dermatol ; 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31343825

RESUMO

BACKGROUND: Standardized skin surface biopsy (SSSB) is often performed to determine the density of Demodex mites in facial papulopustular eruptions. AIM: We aimed to test the applicability of a new, "superficial needle-scraping" (SNS) method for assessing Demodex density in papulopustular rosacea (PPR). PATIENTS AND METHODS: Using SNS method, we measured the Demodex density in patients with PPR, also enrolling the patients with acne vulgaris as controls. SNS was performed by gently scraping off 5 small pustules with the convex surface of the tip of an 18# needle for examination. For comparison, SSSB was also performed in patients with PPR. Demodex density was expressed as "mites per 5 pustules" for SNS and as "mites per cm2 " for SSSB. RESULTS: A total of 40 patients with PPR and 35 patients with acne vulgaris were recruited. There were no statistically significant differences in age or sex between the PPR and acne groups. The Demodex density was 5.6 ± 4.2 in the PPR group versus 0.3 ± 1.0 in the acne group (P < .001). The cutoff of "≥3 Demodex mites per 5 pustules" gave a sensitivity of 78% and a specificity of 97%, and the area under the receiver operating characteristic curve was 0.89. Moreover, SNS and SSSB gave mutually concordant results (positive or negative) in half of the patients. CONCLUSION: Our study suggests that SNS is a simple and convenient method for assessing Demodex density of pustules in PPR and can be a useful alternative or addition to SSSB for evaluation of Demodex-associated facial papulopustular eruptions.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31263717

RESUMO

The aim of this study was to evaluate if amniotic fluid (AF) mixed with artificial tears or soaked with a soft contact lens (SCL) as a treatment for severe dry eye disease (DED) would improve its signs or symptoms. In this retrospective pilot study 22 consecutive eyes of 11 patients with level 3 DED classified by DEWS 1 (Dry Eye WorkShop 1 2007), were included in the study between June 1 and September 30 in 2017. The study was conducted before DEWS II (Dry Eye WorkShop II 2017), which was published in October 2017. Therefore, DEWS II was not adopted for this study. Soft Contact Lens Acuvue Oasys of Plano with 8.8 base curve and 14 mm diameters by Johnson and Johnson were used to soak in FloGraft, which is an AF, for 30 minutes before placing in 12 eyes in Group 1. The contact lenses were placed in the left eye for 1 week. In Group 2, 10 eyes used 6 mL of artificial tears mixed with 0.25 mL of AF, which were applied to the eye four times a day for 1 week. No other eye medications were used. The eyes that were included had diffuse punctate staining and fast tear breaking times of <5 seconds with severe ocular symptoms (DEWS 1 level 3-4). Photos of fluorescein stain corneas before the treatment and 1 week after the treatment were used to compare the distribution of punctate staining as the objective outcomes for signs. Several questions adopted from the Ocular Surface disease Index (OSDI) about subjective symptoms before and after the treatment were asked, and documented on the chart. Improvement either in symptoms or signs or both of DED after 1 week at follow-up examination was recorded. Group 1, with SCL 46% had improvement after 1 week and Group 2, with artificial tears 50% had improvement after 1 week. Improvement means either symptom relief or comparatively decreased distribution of punctate staining on the cornea or both. No cases had inflammation, infection, irritation or blurred vision. We concluded that FloGraft as an AF can safely improve the symptoms or the signs of severe DED either as a mix with artificial tears or soaked with SCL by about 50% in this case series without evidence of irritation, inflammation or blurred vision in the short term.

11.
Int J Ophthalmol ; 12(5): 858-861, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31131250

RESUMO

The multiple regression formulas and correlation of ocular components with refractive errors are presented by Gaussian optics. The refractive error changing rate for the cornea and lens power, the axial length, anterior chamber depth (ACD) and vitreous chamber depth (VCD) are calculated, including nonlinear terms for more accurate rate functions than the linear theory. Our theory, consistent with the empirical data, shows that the Pearson correlation coefficients for spherical equivalent (SE) and ocular components are highest for SE with axial length, ACD and VCD and weakest for corneal power, lens power and lens thickness. Moreover, our regression formulas show the asymmetric feature of the correlation that the axial length, ACD and VCD are more strongly correlated (with higher negative regression constants) with refractive errors in eyes with hyperopia than in eyes with myopia, particularly for severe hyperopia.

12.
J Cosmet Dermatol ; 18(6): 2011-2018, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31033173

RESUMO

BACKGROUND: Polysaccharopeptides (PSPs) extracted from Trametes versicolor show antitumor, anti-inflammatory, and immunomodulation effects. According to our previous report, the enzymatic hydrolysates obtained from T versicolor PSPs by 80 U/mL ß-1,3-D-glucanase (PSPs-EH80) did not change the functional groups of PSPs but enhanced their antioxidative activities. However, the mechanism elevating the antioxidant and anti-inflammatory effect of PSPs-EH80 is not clear. AIMS: This research focused on the protective mechanism(s) of PSPs-EH80 against free radical and 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced oxidative damage in human keratinocyte (HaCaT) cells. METHODS: We evaluated the anti-inflammatory potential of PSPs-EH80 by assessing its free radical-induced oxidative damage. Using the HaCaT cell as the experimental system, we tested the protective effects of PSPs-EH80 on a model of AAPH-induced cellular oxidative damage through the assessment of cell survival rate. Heme oxygenase 1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nrf2), cyclooxygenase-2 (COX-2), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase were determined using MTT assays and Western blotting. RESULTS: We demonstrated that PSPs-EH80 significantly enhanced keratinocyte viability, and augmented the antioxidant HO-1 expressions through upregulation of the Nrf2, compared with PSPs. Furthermore, PSPs-EH80 significantly reduced AAPH-induced COX-2 expressions through downregulation of the ERK, p38, and NF-κB signaling pathways. CONCLUSION: The PSPs-EH80 exhibits a stronger antioxidant and anti-inflammatory capacity than PSPs. Therefore, PSPs-EH80 could be effective for attenuating free radical-induced oxidative damage in human skin and can be applied widely in the fields of cosmetics and medicine.

13.
J Invest Dermatol ; 139(10): 2204-2214.e7, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30986375

RESUMO

Tumor endothelial marker 1 (TEM1), also known as endosialin or CD248, is a type I transmembrane glycoprotein containing a C-type lectin-like domain. It is highly expressed in pericytes and fibroblasts. Dermal fibroblasts play a pivotal role during cutaneous wound healing, especially in the proliferative phase. However, the physiological function of TEM1 in wound healing is still undetermined. During the process of wound healing, the expression of both TEM1 and platelet-derived growth factor (PDGF) receptor α was highly upregulated in myofibroblasts. In vivo, fibroblast activation and collagen deposition in granulation tissues were attenuated, and wound healing was retarded in TEM1-deleted mice. In vitro, the migration, adhesion, and proliferation of NIH3T3 cells were suppressed following TEM1 knockdown by short hairpin RNA. In PDGF-BB-treated NIH3T3 cells, the downstream signal and mitogenic, and chemoattractive effects were inhibited by TEM1 knockdown. In addition, TEM1 and PDGF receptor α were colocalized in subcellular organelles in fibroblasts, and the association of TEM1 and PDGF receptor α was demonstrated by coimmunoprecipitation. In summary, these findings suggested that TEM1, in combination with PDGF receptor α, plays a critical role in wound healing by enhancing the mitogenic and chemoattractive effects of PDGF-BB and collagen deposition in myofibroblasts.

14.
Dermatol Ther ; 32(3): e12867, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30834614

RESUMO

Giant condyloma acuminatum (GCA), also known as Buschke -Löwenstein tumor, is a huge, rapidly growing variant of condyloma found in the anogenital region. Extragenital GCA is rare and, in most cases, affecting the intertriginous area and treated by excision. We described a case of refractory extragenital GCA involving the large part of the left axilla area successfully treated with immunotherapy and podophyllotoxin. Considering the large size and the location, the lesions were not treated by wide excision because it might result in scar contracture with limitation of shoulder movement or axillary web syndrome. Our case illustrates that combination therapy of podophyllotoxin, imiquimod plus weekly cryotherapy may be an effective and less invasive option for treating GCA of the axilla with good cosmetic and functional outcomes.


Assuntos
Axila/patologia , Tumor de Buschke-Lowenstein/terapia , Neoplasias Cutâneas/terapia , Adulto , Tumor de Buschke-Lowenstein/patologia , Terapia Combinada , Crioterapia/métodos , Humanos , Imiquimode/administração & dosagem , Imunoterapia/métodos , Masculino , Podofilotoxina/administração & dosagem , Neoplasias Cutâneas/patologia , Resultado do Tratamento
16.
Sci Rep ; 9(1): 3395, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30833579

RESUMO

Derailed transmembrane receptor trafficking could be a hallmark of tumorigenesis and increased tumor invasiveness, but receptor dynamics have not been used to differentiate metastatic cancer cells from less invasive ones. Using single-particle tracking techniques, we  developed a phenotyping asssay named Transmembrane Receptor Dynamics (TReD), studied the dynamics of epidermal growth factor receptor (EGFR) in seven breast epithelial cell lines and developed a phenotyping assay named Transmembrane Receptor Dynamics (TReD). Here we show a clear evidence that increased EGFR diffusivity and enlarged EGFR confinement size in the plasma membrane (PM) are correlated with the enhanced metastatic potential in these cell lines. By comparing the TReD results with the gene expression profiles, we found a clear negative correlation between the EGFR diffusivities and the breast cancer luminal differentiation scores (r = -0.75). Upon the induction of epithelial-mesenchymal transition (EMT), EGFR diffusivity significantly increased for the non-tumorigenic MCF10A (99%) and the non-invasive MCF7 (56%) cells, but not for the highly metastatic MDA-MB-231 cell. We believe that the reorganization of actin filaments during EMT modified the PM structures, causing the receptor dynamics to change. TReD can thus serve as a new biophysical marker to probe the metastatic potential of cancer cells and even to monitor the transition of metastasis.

18.
Ann Plast Surg ; 82(1S Suppl 1): S39-S44, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30461461

RESUMO

BACKGROUND: Surgical excision with adjuvant radiotherapy has gained attention as an effective treatment of keloid. The Asian population is challenged with a high incidence of keloid occurrence with a specific genetic predominance. The annual reported incidence of new keloid cases in Taiwan is around 30,000, but the disease control rate and effectiveness by means of surgical excision with adjuvant radiotherapy is not yet clear. METHODS: A retrospective chart review of the included consecutive keloid patients receiving surgical excision and radiotherapy was performed from 2013 to 2016 in a single institute. The reported risk factors were collected to investigate according to the outcome analysis. The Vancouver Scar Scale and the Japan Scar Workshop (JSW) Scar Scale were used to evaluate the correlation with keloid recurrence. RESULTS: In this series, the overall recurrence rate was 32%, reported with an average follow-up of 28 months. Independent risk factors varied according to the different outcome variables. Only JSW classification score independently predicted the risk of keloid recurrence (odds ratio, 1.305; P = 0.02). Both the Vancouver Scar Scale and the JSW system showed a good correlation with keloid recurrence (correlation efficiency, 0.529 and 0.54; P = 0.0437 and 0.0165, respectively). CONCLUSIONS: This preliminary report revealed convincing evidence of feasibility and effectiveness of applying adjuvant radiotherapy after keloid excision in the Taiwanese population. A more delicate biological equivalent dose of radiotherapy with an effective local control should be considered to improve the final outcome.

19.
Clin Pharmacol Ther ; 105(1): 112-120, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29569740

RESUMO

Specific ethnic genetic backgrounds are associated with the risk of Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN) especially in Asians. However, there have been no large cohort, multiple-country epidemiological studies of medication risk related to SJS/TEN in Asian populations. Thus, we analyzed the registration databases from multiple Asian countries who were treated during 1998-2017. A total 1,028 SJS/TEN cases were identified with the algorithm of drug causality for epidermal necrolysis. Furthermore, those medications labeled by the US Food and Drug Administration (FDA) as carrying a risk of SJS/TEN were also compared with the common causes of SJS/TEN in Asian countries. Oxcarbazepine, sulfasalazine, COX-II inhibitors, and strontium ranelate were identified as new potential causes. In addition to sulfa drugs and beta-lactam antibiotics, quinolones were also a common cause. Only one acetaminophen-induced SJS was identified, while several medications (e.g., oseltamivir, terbinafine, isotretinoin, and sorafenib) labeled as carrying a risk of SJS/TEN by the FDA were not found to have caused any of the cases in the Asian countries investigated in this study.


Assuntos
Grupo com Ancestrais do Continente Asiático , Rotulagem de Medicamentos/normas , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/epidemiologia , United States Food and Drug Administration/normas , Alopurinol/efeitos adversos , Anti-Infecciosos/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Anticonvulsivantes/efeitos adversos , Antipsicóticos/efeitos adversos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Coortes , Depuradores de Radicais Livres/efeitos adversos , Humanos , Sistema de Registros , Fatores de Risco , Síndrome de Stevens-Johnson/genética , Estados Unidos/epidemiologia
20.
Exp Dermatol ; 28(4): 464-471, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29105155

RESUMO

Following skin wounding, the healing outcome can be: regeneration, repair with normal scar tissue, repair with hypertrophic scar tissue or the formation of keloids. The role of chemical factors in wound healing has been extensively explored, and while there is evidence suggesting the role of mechanical forces, its influence is much less well defined. Here, we provide a brief review on the recent progress of the role of mechanical force in skin wound healing by comparing laboratory mice, African spiny mice, fetal wound healing and adult scar keloid formation. A comparison across different species may provide insight into key regulators. Interestingly, some findings suggest tension can induce an immune response, and this provides a new link between mechanical and chemical forces. Clinically, manipulating skin tension has been demonstrated to be effective for scar prevention and treatment, but not for tissue regeneration. Utilising this knowledge, specialists may modulate regulatory factors and develop therapeutic strategies to reduce scar formation and promote regeneration.

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